​During my training I think I’ve been steered to think of 0.9% saline as akin to the devil, causing hyperchloraemic acidosis in all it touches – is that true?

It is perhaps a slight exaggeration, as I accept it has benefits in certain circumstances and has less adverse effects in small volumes. From observational studies we are aware that large volumes of 0.9% saline have been linked to changes in renal physiology and to the development of AKI in ICU patients.

In Dec 2014 our Australian colleagues Yunos et al. published an extended analysis of their original study looking at chloride-containing fluids and the incidence of AKI in ICU. The original study considered two consecutive 6-month study periods, the first being a period of unrestricted fluids as a control, and a second when chloride-containing fluids were restricted (0.9% saline, 4% albumin, gelatin). The extended analysis used similar methodology but the time periods were each 12 months. Although these studies have each been subject to some criticism, both papers concluded that there was a higher incidence of AKI and RRT in the control groups. The extended study also suggested that there were other unidentified confounders which may have contributed to the incidence of AKI.

This study (the SPLIT trial), published in October’s JAMA, aimed to provide further insight into the development of AKI after administration of 0.9% saline and buffered crystalloid solutions in a broad range of ICU patients.

What and where:

The authors published their proposed study protocol in ‘Intensive Care’ last year. The prospective, double-blinded cluster randomised (i.e. they looked at groups of patients rather than individuals) double cross-over (so each group received both the control and intervention, twice) study was conducted between Apr-Oct 2014.

Objective: To determine the effect of a buffered crystalloid compared with saline on renal complications in patients admitted to the ICU

No fixed sample size (defined study period and there is no established statistical methodology for prospective cluster randomised, double-crossover studies with binary outcome variables - therefore this was a feasibility study).

Serum chloride levels were not included and so we don’t know if any patients developed hyperchloraemic acidosis and AKI. Hence, doesn’t help clarify if hyperchloraemic acidosis leads to AKI

High risk groups under represented and therefore unknown benefit/harm for this population (mean APACHE II 14 and majority elective post-op)

Low background mortality in the study population reduces the power for a clinically important change in mortality.

Unable to consider a sub-clinical effect.

Not an effectiveness trail but a feasibility study for future work.

So what?The take home message from this paper is that in small volumes (approximately 2L) of 0.9% saline and Plasma-Lyte do not cause AKI or increase mortality in low-moderate risk patients. This is great, but the discussion points below need to be considered:

Plasma-Lyte was chosen as the buffered crystalloid in this study due the preference of this over Hartmann’s and CSL in the ICU’s studied. In our ICU we use CSL, which although similar, does have significant differences to Plasma-Lyte. Firstly, it should be pointed out that no solution is ‘physiological’, however Plasma-Lyte has the benefit of being more isotonic and containing less chloride. However, Plasma-Lyte does contain acetate, which has been shown to cause vasodilatation and is pro-inflammatory. Also, sodium gluconate may act as an osmotic diuretic. It is not an absolute given to assume the study can be translated to Hartmann’s solution or CSL.

Sepsis is the main reason for admission to ICU in the UK but few patients with sepsis were included in the study. Sepsis-induced AKI has a different pathophysiology to other causes of renal injury and therefore potentially changes the susceptibility to AKI.

Many of the patients we admit have either received large volumes of IVT on the wards/ED or require fluid resuscitation greater than 2L of crystalloid.

The typical Sunderland patient often has multiple significant co-morbidities, unlike the study population, again potentially increasing their susceptibility to AKI.